In vivo genotoxicity of ortho-phenylphenol, biphenyl, and thiabendazole detected in multiple mouse organs by the alkaline single cell gel electrophoresis assay.
In Japan, ortho-phenylphenol (OPP), biphenyl (BP), and thiabendazole (2-(4'-thiazolyl)benzimidazole, TBZ) are commonly used as a postharvest treatment to preserve imported citrus fruits during transport and storage. We used a modification of the alkaline single cell gel electrophoresis (SCG) (Comet) assay to test the in vivo genotoxicity of those agents in mouse stomach, liver, kidney, bladder, lung, brain, and bone marrow. CD-1 male mice were sacrificed 3, 8, and 24 h after oral administration of the test compounds. OPP (2000 mg/kg) induced DNA damage in the stomach, liver, kidney, bladder, and lung, BP (2000 mg/kg) and TBZ (200 mg/kg) induced DNA damage in all the organs studied. For OPP, increased DNA damage peaked at 3-8 h and tended to decrease at 24 h. For BP, on the contrary, increased DNA migration peaked at 24 h. That delay may have been due to the fact that OPP is metabolized by cytochrome 450 and prostaglandin H synthase to phenylbenzoquinone (PBQ), a DNA binding metabolite, and BP is metabolized to PBQ via OPP and m-phenylphenol. The positive response to TBZ, an aneugen, supports the in vivo DNA-damaging action of TBZ.
Sasaki
Y F
YF
Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology, Aomori, Japan. yfsasaki-c@hachinohe-ct.ac.jp
Saga
A
A
Akasaka
M
M
Yoshida
K
K
Nishidate
E
E
Su
Y Q
YQ
Matsusaka
N
N
Tsuda
S
S
D000818:Animals; D001713:Biphenyl Compounds / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004249:DNA Damage; D004586:Electrophoresis / Q000379:methods*; D005659:Fungicides, Industrial / Q000633:toxicity; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests / Q000379:methods*; D013270:Stomach / Q000187:drug effects; D013827:Thiabendazole / Q000633:toxicity*; D013997:Time Factors; D014018:Tissue Distribution
D001713:Biphenyl Compounds; D005659:Fungicides, Industrial; D013827:Thiabendazole; C010574:biphenyl; C004369:2-phenylphenol